The long-term goal of this Program Project is to identify individual genes that contribute to variation in susceptibility to coronary heart disease (CHD) in Mexican Americans. Hispanics are the fastest growing minority population in the United States and will soon be our largest minority group. This population has a high prevalence of CHD and of other disorders that adversely affect the lipoprotein profile, particularly non-insulin- dependent diabetes mellitus (NIDDM) and obesity. Nevertheless, very few genetic studies of intervening variables for CHD have been directed at this population, and the relationships among CHD, NIDDM and obesity remain poorly understood for any human population. This Program Project will focus on genes that influence the lipoprotein profile in members of randomly ascertained Mexican-American families, with particular emphasis on genetic effects on reverse cholesterol transport. An overall objective is to investigate the pleiotropic effects of these "lipoprotein genes" and their interactions with genes that affect NIDDM antecedents and body fat distribution. The interactions of lipoprotein genes with sex hormonal status and with environmental risk factors such as diet, exercise, and smoking will be investigated. Genetic effects on standard lipoprotein variables will be examined, e.g. plasma concentrations of lipoproteins and apolipoproteins. Several novel lipoprotein phenotypes also will be analyzed, e.g. amounts of esterified and unesterified cholesterol and of specific apolipoproteins in lipoprotein subclasses. Molecular, biochemical, and statistical genetic approaches will be used to detect, localize and characterize genes that influence quantitative phenotypes associated with lipoproteins, NIDDM, and obesity, and to quantify the effects of known candidate loci on these phenotypes.